The essentiality of the trace element zinc is anchored in its role as a cofactor in a number of enzymes and in its function as a signaling molecule. Among other cell systems, the immune system requires zinc for adequate functionality. Not only zinc deprivation but also exceedingly high zinc levels result in immune dysfunction, depicting the significance of a regulated zinc homeostasis for the immune response. Disturbances of zinc homeostasis affect multiple aspects of the immune system, including hematopoiesis, innate immunity, adaptive immune response and processes involved in immune regulation. Zinc deficiency impairs the development of lymphocyte progenitors and modifies the differentiation of cells of the innate immune system. Furthermore, immune cell function is adversely affected during zinc deprivation, resulting in compromised lymphocyte immune reaction combined with dysregulated innate immune responses. Consequently, the development and progression of various infections and diseases is influenced by alterations in the zinc homeostasis. For several decades, the immunobiology of zinc has been studied. This chapter aims to discuss the overall impact of zinc on the immune system.